Urinary nitrate excretion in cholesterol-fed rabbits: effect of a chronic treatment by N-iminoethyl-L-lysine, a selective inhibitor of inducible nitric oxide synthase

To evaluate the influence of atherosclerosis on the global production of NO , we studied the effect of a 0.3% cholesterol-enriched diet on urinary nitr ate excretion in rabbits during 69 weeks. To examine whether the inducible nitric oxide synthase (iNOS) present in atherosclerotic lesions could parti cipate in NO excretion, hypercholesterolemic rabbits were treated chronical ly with the selective iNOS inhibitor, N-iminoethyl-L-lysine (L-NIL; 5 mg/kg /day). Urinary nitrate excretion was higher in hypercholesterolemic than in control rabbits throughout the study period and decreased progressively wi th time in both groups; L-NIL had no significant effect on urinary nitrate excretion. These data illustrate that systemic NO production is enhanced in hypercholesterolemia and that iNOS, present within the plaque, might not p articipate in this enhanced NO production. (C) 2000 Elsevier Science B.V. A ll rights reserved.